We determined the distribution coefficients of solutes between a polymer film phase (polyvinyl chloride (PVC) with 67% (w/w) dioctyl sebacate (DOS)) and an aqueous phase in a 96-well format. The parallel measurement approach is efficient and uses very little material. Polymer-water distribution coefficients (Dpw) at different pH values yield the pKa and polymer-water partition coefficient values (Ppw) of the solutes. Log Ppw of a prominent drug-like compound, 2H-1, 2, 6-thiadiazine, 3-methyl-5-phenyl-, 1, 1-dioxide, is in good agreement with cLogP, while the pKa value is substantially different from calculated values. This method has been also successfully applied to a library of novel drug-like compounds. Log Dpw values (at pH 4.0, 7.0, 10.0) of 24 novel drug-like compounds have been determined with good reproducibility with the 96-well plate approach. Differences between experimental values and a variety of available calculated values are significant. This emphasizes the need for laboratory separations-based measurements of logD.